Primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is a long-term liver disease in which the bile ducts in the liver become damaged.
This gradually leads to a build-up of bile in the liver, which can damage it and eventually lead to scarring (cirrhosis).
PBC doesn't always cause any symptoms in the early stages, but some people may experience:
fatigue (extreme tiredness)
dry eyes and mouth
pain or discomfort in the upper right corner of their tummy
Many people are only diagnosed with PBC after a problem with their liver is picked up during a routine blood test that is carried out for another reason.
What causes PBC?
Bile is a liquid produced inside the liver that is used to help digest fats and remove toxins from the body. It passes out of the liver through small tubes called bile ducts.
In PBC, for reasons not fully understood, the immune system (the body's natural defence against infection and illness) mistakenly attacks the bile ducts.
This gradually causes the bile ducts to become swollen and scarred, obstructing the flow of bile out of the liver. Bile then starts to build up in the liver, which damages it and may lead to cirrhosis.
Who is affected
It's not clear how many people are affected by PBC in the UK. Estimates vary from around 15,000 to 20,000 people.
The rates of PBC in the UK are higher than in some other parts of the world. The reason for this is unknown.
About 90% of those affected are women and most cases are diagnosed in people aged 40-60, although PBC can be diagnosed at any age from 20 onwards.
How PBC is treated
PBC is a progressive condition, which means the damage to the liver can get steadily worse over time. The rate at which PBC progresses varies between individuals. In some cases, it can take decades.
If not treated, the liver can become damaged to such an extent that it no longer works properly. This is known as liver failure and it can be fatal.
There are medications that can help slow the progression of the condition and help relieve the itchiness associated with it. In cases where there is extensive liver damage, a liver transplant may be required.
Symptoms of primary biliary cirrhosis
Primary biliary cirrhosis (PBC) often doesn't cause any symptoms in the early stages and many people are only diagnosed with the condition during tests carried out for another reason.
People who do have symptoms may experience:
fatigue (extreme tiredness) – this is the most common symptom, and can have a significant impact on your daily activities
itchy skin– this can be widespread or it can only affect a single area; it may be worse at night, when in contact with fabrics, when warm, or during pregnancy
dry eyes and mouth
problems sleeping at night and feeling very sleepy during the day
pain or discomfort in the upper right corner of the tummy
dizziness when standing up (postural or orthostatic hypotension)
Some people may also have symptoms of conditions that often occur alongside PBC, such as an underactive thyroid (hypothyroidism).
For unknown reasons, there is often little association between the severity of symptoms and the degree of underlying liver damage. Some people with PBC have severe symptoms even though tests show that their liver is not severely damaged, while tests may reveal that others with no or mild symptoms may have significant liver damage.
Medication can usually help to delay liver damage in people with PBC, but if the liver does become extensively damaged (cirrhosis), you may have additional symptoms.
These can include:
jaundice (yellowing of the skin and whites of the eyes)
a build-up of fluid in the legs, ankles and feet (oedema)
build-up of fluid in your tummy that can make you look heavily pregnant (ascites)
the formation of small fatty deposits on the skin, usually around your eyes (xanthelasmata)
dark urine and pale stools
a tendency to bleed and bruise more easily
problems with memory and concentration
Causes of primary biliary cirrhosis
The exact cause of primary biliary cirrhosis (PBC) is unknown, although it is widely thought to be the result of a problem with the immune system.
Most experts believe that PBC is an autoimmune condition. This means that something goes wrong with the immune system (the body's natural defence against infection and illness) and it attacks healthy tissue instead of fighting off infection.
In cases of PBC, the immune system sends specialised cells that usually kill bacteria and viruses to the bile ducts.
These cells damage the surface of the bile ducts, which gradually become scarred and disrupt the flow of bile out of the liver. This increases the amount of bile in the liver, which over time can cause it to also become extensively damaged and scarred (cirrhosis).
This damage can gradually cause the liver to lose its function. As the liver plays a vital role in filtering out impurities and toxins from your blood, loss of liver function is potentially fatal.
It is not known what causes the immune system to malfunction and attack the bile ducts.
Other autoimmune conditions
People with PBC are often more likely to also have another autoimmune condition. For example, they may also have:
where the thyroid gland does not produce enough hormones
a condition that causes pain and swelling in the joints
a condition that affects connective tissue (the supporting tissues of the body), causing hard, puffy and itchy skin
autoimmune a very rare cause of long-term hepatitis, where the immune system attacks the liver
a condition in which the immune system attacks the body's tear and saliva glands
a common condition that affects the blood supply to certain parts of the body, usually the fingers and toes
a common digestive condition where a person has an adverse reaction to gluten because the immune system mistakes substances found inside gluten as a threat to the body
Although the reason why some people develop PBC is not clear, it's thought that your genes may make you more susceptible to developing the condition and that it is triggered by something else.
There is some evidence to suggest that certain things can increase your chances of developing PBC. These are explained below.
PBC occurs mostly in women. Less than one in 10 cases of PBC occur in men.
One theory for this is that the immune system may be affected by the female sex hormone, oestrogen.
Having a close relative with PBC means you are more likely to develop the condition yourself.
For example, if you are female and your mother has or has had PBC, you are much more likely to develop PBC than someone who has no relatives with the condition. However, the risk is still low.
Certain things may trigger PBC in people with a genetic tendency. These include:
infections – such as a urinary tract infection (UTI)
hormone replacement therapy (HRT) – a treatment used to replace the female hormones that a woman's body no longer produces because of the menopause
using nail varnish or cosmetics
smoking cigarettes or having a history of heavy smoking
living near to where toxic waste has been dumped
However, none of these have been proven as definite triggers of PBC. Most people who are exposed to them will not develop the condition. There is nothing to suggest that you should reduce your exposure to these triggers to lower your risk of developing PBC.
Diagnosing primary biliary cirrhosis
In many cases, a suspected diagnosis of primary biliary cirrhosis (PBC) is made after having a blood test for another, unrelated condition.
Damage to the bile ducts and liver leads to an increase in enzymes produced by your liver. The high level of enzymes can be detected by certain routine blood tests.
A diagnosis of PBC can usually be confirmed by checking your blood for anti-mitochondrial antibodies (AMAs). In PBC, AMAs are produced by the immune system (the body's natural defence against infection and illness). They are present in around 95% of people with PBC.
You may also have a high level of bilirubin in your blood. Bilirubin is a yellow substance produced when red blood cells are broken down. The liver usually "takes up" bilirubin from the blood and it is passed out of your body in urine.
If there is something wrong with your liver or bile ducts, bilirubin cannot be moved into the bowel and leaks back out into the blood. This shows up on a blood test.
You may also have an ultrasound scan to help rule out other problems with your bile ducts, such as a blockage caused by bile duct stones.
This is a painless scan, similar to the scan carried out during pregnancy, that involves using a probe that emits high-frequency sound waves to create an image of the inside of your tummy.
An ultrasound scan can also be used to assess the stiffness of your liver and identify any scarring (cirrhosis).
You may sometimes be referred for a liver biopsy. This involves removing a small sample of liver tissue so it can be studied under a microscope.
Most liver biopsies can be carried out under local anaesthetic to numb your skin. The sample is obtained using a long needle inserted through your tummy.
A liver biopsy is not always necessary to diagnose PBC, because it is usually confirmed by the presence of AMAs, but it can be used to assess the extent of damage to your liver and, increasingly, suggest the right treatment for you.
Treating primary biliary cirrhosis
The aim of treatment for primary biliary cirrhosis (PBC) is to prevent liver damage as much as possible and reduce your symptoms.
All types of liver disease, including PBC, can be helped by following some general health advice. You should:
maintain a healthy weight
not drink more than the recommended daily limits of alcohol (3-4 units a day for men, and 2-3 units a day for women)
Not following this advice could speed up the progression of your condition. It may also affect whether you can have a liver transplant, if you need one. For example, you may not be offered a liver transplant if you drink more than the recommended daily limits of alcohol.
Avoid certain medications
Besides the medications below, you should also be careful about taking some medicines if you have PBC because the damage to your liver can affect its ability to process certain medications.
For example, you may need to avoid non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, although paracetamol can usually be taken safely.
Ask your doctor about any medications you should avoid and inform any health professional who is treating you that you have PBC, particularly if they suggest taking medication.
Ursodeoxycholic acid (UDCA) is the main treatment for people with PBC. It can help prevent or delay liver damage in most people –particularly if you start taking it in the early stages of the condition –although it doesn't improve symptoms such as itchy skin or fatigue (extreme tiredness).
Once you start taking UDCA, it is likely you will need to take it for the rest of your life. Regular blood tests may be carried out to monitor your liver function and you will be assessed after a year to see if you have responded sufficiently. If not, you may need additional treatment.
One possible side effect of UDCA is weight gain. People gain an average of 2.3kg (5lbs) during the first year of taking the medication, although most people don't gain any more weight after this.
Other side effects can include diarrhoea, nausea, vomiting and thinning hair.
Colestyramine (previously called cholestyramine) is a medicine widely used to treat the itchiness associated with PBC.
It usually comes in sachets of a powder that can be dissolved in water or fruit juice. It is a good idea to take the powder with fruit juice, because it has an unpleasant taste.
You may need to take colestyramine for several days before your symptoms begin to improve.
If you are taking UDCA as well as colestyramine, you should avoid taking them at the same time because colestyramine will affect how your body absorbs UDCA. You should take UDCA at least one hour before colestyramine, or four to six hours afterwards.
This also applies to any other medicines you are taking. Your GP can give you further advice about this.
Constipation is a common side effect of colestyramine, although this usually improves once your body gets used to the medicine. Other side effects can include bloating and diarrhoea.
If you are taking colestyramine on a long-term basis, the medicine may affect your body's ability to absorb vitamins A, D and K from food. In such cases, taking additional vitamin supplements may be beneficial. Your GP can advise you on whether you would benefit from taking vitamin supplements.
Alternative treatments for itching
See your GP if your itchiness does not improve after taking colestyramine. Alternative medicines are available, such as an antibiotic called rifampicin and a medication called naltrexone.
These are usually only prescribed by a specialist such as a hepatologist (liver specialist), but your GP can refer you if necessary.
It's thought that the female hormone oestrogen may make itching worse. Oestrogen is found in some types of hormonal contraceptives, such as the combined contraceptive pill. Therefore, you may want to consider using a different type of contraceptive, such as condoms.
Regularly using moisturisers to stop your skin becoming dry may also help reduce itchiness.
At the moment, no medications are available to specifically treat the fatigue caused by PBC. Your GP may want to rule out and treat any other possible causes for your tiredness, such as anaemia (a lack of red blood cells) or depression, as fatigue is a difficult symptom to treat.
You should try to exercise whenever possible, but you may need to pace yourself and limit your daily activities to a manageable level. Adjusting your daily routine around fatigue (which is often worse later in the day) can make a big difference to your quality of life.
If you have difficulty sleeping, sleep hygiene measures may help. These include avoiding caffeine, nicotine and alcohol late at night, and maintaining a comfortable sleeping environment.
Treating dry mouth and eyes
If you have a dry mouth and eyes, your GP may recommend eye drops containing "artificial tears" or saliva substitute products.
You should also make sure you maintain a good standard of oral hygiene and visit your dentist regularly because having a dry mouth can increase your risk of tooth decay.
A liver transplant may be recommended if it's thought that the liver damage may eventually reach the stage where your life is at risk.
Planning for a liver transplant often begins before significant damage to the liver has taken place because:
the average waiting time for a liver transplant is 145 days, so it's important to start searching for a suitable donor as soon as possible
the better your general state of health, the greater the chance of a successful transplant, so a transplant should ideally be carried out while you are still relatively healthy
Having a liver transplant resolves a number of symptoms, most typically itchiness. Fatigue, however, is usually persistent.
Like all organ transplants, liver transplants carry a risk of complications. One of the most serious complications is that your immune system may reject the donated liver, which could be life-threatening. You will usually need to take medication to suppress your immune system for the rest of your life to reduce this risk.
The success rates of liver transplants for people with PBC are generally better than most other liver diseases. Studies have found that more than 90% of people who have a liver transplant for PBC are still alive after a year and more than 80% will live at least another five years.
There is a risk of PBC developing in your new liver, but this isn't usually a major concern because it often takes a long time to develop.
Complications of primary biliary cirrhosis
If primary biliary cirrhosis (PBC) is not treated or reaches an advanced stage, it can cause other potentially serious problems.
For reasons that are unknown, people with PBC are at an increased risk of developing osteoporosis. This is a condition in which the bones become weak and brittle.
A DEXA scan, which is a type of X-ray that measures the density of your bones, may be carried out when you are diagnosed with PBC and regularly thereafter to monitor the condition of your bones.
Your GP may prescribe vitamin D and calcium supplements to help maintain your bone strength.
You may also be advised to exercise regularly, with a particular focus on weight-bearing exercises such as running, dancing and aerobics, because this can help reduce your risk of osteoporosis.
In some cases, you may also need more specific treatment, such as bisphosphonates. This is a medication that slows the rate at which bone is broken down by the body, which can help maintain bone density and reduce the risk of a fracture.
Portal hypertension and varices
Portal hypertension is increased blood pressure inside your liver as a result of damage and scarring (cirrhosis), making it harder for blood to move through it.
For your blood to return from your liver to your heart, new blood vessels start to open up, usually along the lining of your stomach or oesophagus (the long tube that carries food from the throat to the stomach). These new blood vessels are known as varices.
The walls of these varices are quite fragile and in some cases can split open and bleed.
This can cause gradual, long-term bleeding, which can lead to anaemia(a lack of red blood cells), or it can be sudden and severe, causing you to vomit blood and pass stools that are very dark or tar-like.
If you vomit blood or have very dark stools, you should go to your local GP surgery or your nearest accident and emergency (A&E) departmentimmediately.
Portal hypertension can sometimes be managed with a type of medication known as beta blockers, which can help reduce your blood pressure, although a procedure to seal the varices using an endoscope(a narrow tube with a camera at the end that is passed down your throat) may be recommended in some cases.
If you have portal hypertension, you may also develop a build-up of fluid in your abdomen (stomach) and around your intestines. This fluid is known an ascites.
Initially, this can be treated with water tablets (diuretics). If the problem progresses, many litres of fluid can build-up and this will need to be drained. This is a procedure known as paracentesis and involves a long thin tube being placed into the fluid through the skin under local anaesthetic.
One of the problems associated with ascites is the risk of infection in the fluid (spontaneous bacterial peritonitis). This is potentially a very serious complication and can be fatal.
One of the most important functions of the liver is to remove toxins from your blood. If your liver is unable to do this due to cirrhosis, the levels of toxins in your blood can increase and lead to a condition called hepatic encephalopathy.
Symptoms of hepatic encephalopathy can include:
in very serious cases, coma
Hepatic encephalopathy may require admission to hospital. In hospital, your body functions will be supported while medication is given to remove the toxins from the blood.
Hepatic encephalopathy is very uncommon in PBC and must be distinguished from concentration and memory problems linked to fatigue.
Bile produced by the liver plays an important role in digestion, particularly in digesting fats. As the flow of bile out of the liver is obstructed in people with PBC, the condition may occasionally cause problems absorbing "fat-soluble" vitamins – including vitamins A, D, E and K.
The medication colestyramine, often used to reduce the itchiness associated with PBC, can also affect your body's ability to absorb some of these vitamins from food.
Significant deficiencies in these vitamins can cause problems such as:
difficulty seeing in poor light
reduced bone density (osteopenia)
nerve damage (peripheral neuropathy)
a tendency to bleed or bruise easily
If you're not getting enough of one or more of these vitamins, you doctor may recommend taking supplements.
If you have PBC, the progressive damage to your liver slightly increases your risk of developing liver cancer.
Therefore, regular screening may be recommended to look for signs of cancer because the earlier the cancer is diagnosed, the greater the chance there is of curing it.
Screening will typically involve regular ultrasound scans and blood tests.